The proposed investigation will focus on aspects of squalene biosynthesis. The factors determining substrate recognition have been examined. For example, the C6C7 double bond is essential as is the C3 methyl. The C6 methyl is important for moderate substrate metabolization. The terminal methyl groups are of the least importance. The two binding sites for farnesyl pyrophosphate differ in substrate specificity. The first binding site is the more demanding of the two, regardless of structural modifications at C3, C7, or C12. In view of these constraints, analogues are being designed which can only be partially metabolized. After isolation and identification of the metabolites, we hope to reach some conclusions concerning the nature of the transformation of farnesyl pyrophosphate to squalene.